We have demonstrated peak collagenase activity and collagen synthesis in the liver of mice 8 weeks after infection with Schistosoma mansoni; this time is coincident with the known peak of host cellular immune response and occurrence of macrophage migration inhibitory factor. We have isolated granuloma collagenase and EDTA-sensitive neutral protease and raised antibodies against each purified enzyme. Isolated granuloma collagense anti-IgG and neutral protease anti-IgG react with each respective granuloma enzyme (both active- and inactive-forms) and with the respective isolated liver enzymes or homogenates of livers of infected mice. There is no cross-reaction between antisera to the collagenase or protease and non-corresponding antigen nor do the antisera react with culture medium containing isolated schistosome eggs or normal liver homogenates. In other experiments, we observed decreased liver collagen contents in mice treated with rabbit IgG or aggregated rabbit IgG when compared with control mice. We have also observed reversal of advanced liver fibrosis in rabbits following parasitologically cured Schistosoma japonicum; elevated collagenase activity persisted after diminished collagen synthesis. We plan (1) to identify the cells that produce collagenase by use of immunofluorescent antibody techniques. (2) to determine whether increased collagenase activity (in liver of infected mice) result from modulators, and whether these modulators accordingly can reduce collagen accumulation in fibrosis caused by schistosomiasis.